Document Detail


Therapeutic developments in the treatment of amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  12387699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterised by the selective death of motor neurones. The mechanisms and processes responsible for the selective loss of motor neurones are still unknown, however several hypotheses have been put forward, including oxidative damage and/or toxicity from intracellular aggregates due to mutant superoxide dismutase-1 activity, axonal strangulation from cytoskeletal abnormalities, loss of trophic factor support and glutamate-mediated excitotoxicity. These theories are based on a better understanding of the genetics of amyotrophic lateral sclerosis and on biochemical and pathological analysis of post-mortem tissue. They have led to the development of appropriate animal and cell culture models, allowing the sequence of events in motor neuronal degeneration to be unravelled and potential therapeutic agents to be screened. Unfortunately, the majority of therapeutics found to be efficacious in the animal and cell culture models have failed in human trials. Riluzole is still the only proven therapy in humans, shown to extend survival of amyotrophic lateral sclerosis patients by approximately 3 months, but it has no effect on muscle strength. Other potential therapeutic approaches are being identified, including inhibition of caspase-mediated cell death, maintenance of mitochondrial integrity and energy production, regulation of glutamate homeostasis, reduction of inflammation and control of neurofilament synthesis. Hopefully, in the near future some new agents will be found that can alter the course of this devastating and fatal disease.
Authors:
Mandy Jackson; Jerònia Lladó; Jeffrey D Rothstein
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  11     ISSN:  1354-3784     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-21     Completed Date:  2003-03-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1343-64     Citation Subset:  IM    
Affiliation:
Department of Preclinical Veterinary Sciences, The University of Edinburgh, Scotland, UK.
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MeSH Terms
Descriptor/Qualifier:
Amyotrophic Lateral Sclerosis / drug therapy*,  metabolism,  pathology
Animals
Anti-Inflammatory Agents / therapeutic use
Antioxidants / therapeutic use
Clinical Trials as Topic / statistics & numerical data
Excitatory Amino Acid Antagonists / therapeutic use
Humans
Technology, Pharmaceutical / trends*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antioxidants; 0/Excitatory Amino Acid Antagonists

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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